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Insulin like growth factor-1 increases fatty liver preservation in IGL-1 solution
Mohamed Amine Zaouali, Susagna Padrissa-Altés, Ismail Ben Mosbah, Hassen Ben Abdennebi, Olivier Boillot, Antoni Rimola, Dalila Saidane-Mosbahi, Joan Roselló-Catafau
Mohamed Amine Zaouali, Susagna Padrissa-Altés, Ismail Ben Mosbah, Joan Roselló-Catafau, Experimental Hepatic Ischemia-Reperfusion Unit, Institut d’Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas, 08036 Barcelona, Spain
Mohamed Amine Zaouali, Antoni Rimola, Joan Roselló-Catafau, Unitat de Transplantament de Fetge i Viabilitat de l’Empelt, Institut d’Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain
Hassen Ben Abdennebi, Dalila Saidane-Mosbahi, Laboratory of Human Physiology, Faculty of Pharmacy, University of Monastir, 5000 Monastir, Tunisia
Olivier Boillot, Unit of Hepatic Transplantation, Edouard Herriot Hospital, 69003 Lyon, France
Antoni Rimola, Joan Roselló-Catafau, Biomedical Research Center Esther Koplowitz, CIBER-ehd, Institute of Health Carlos III, 08036 Barcelona, Spain
Author contributions: Zaouali MA, Padrissa-Atés S and Ben Mosbah I carried out the experimental work; Zaouali MA and Ben Abdennebi H provided the protocols and analyzed the data; Ben Abdennebi H, Saidane-Mosbahi D, Boillot O and Rimola A established the experimental animal model used in this study and contributed to the critical analyses of the data; Zaouali MA and Roselló-Catafau J designed the study, coordinated the experiments and wrote the paper.
Supported by The Ministry of Health and Consumption (PI 081988), CIBER-ehd, Carlos III Institute, Madrid, Spain; Ministry of Foreign Affairs and International Cooperation (A/020255/08 and A/02987/09); Mohamed Amine Zaouali is fellowship-holder from the Catalan Society of Transplantation
Correspondence to: Dr. Joan Roselló-Catafau, Experimental Hepatic Ischemia-Reperfusion Unit, IIBB-CSIC, C/Rosellón 161, 7th floor, 08036 Barcelona, Spain. jrcbam@iibb.csic.es
Telephone: +34-93-3638333 Fax: +34-93-3638301
Received: March 15, 2010
Revised: May 15, 2010
Accepted: May 22, 2010
Published online: December 7, 2010
AIM: To investigate the benefits of insulin like growth factor-1 (IGF-1) supplementation to serum-free institut georges lopez-1 (IGL-1)® solution to protect fatty liver against cold ischemia reperfusion injury.
METHODS: Steatotic livers were preserved for 24 h in IGL-1® solution supplemented with or without IGF-1 and then perfused “ex vivo” for 2 h at 37°C. We examined the effects of IGF-1 on hepatic damage and function (transaminases, percentage of sulfobromophthalein clearance in bile and vascular resistance). We also studied other factors associated with the poor tolerance of fatty livers to cold ischemia reperfusion injury such as mitochondrial damage, oxidative stress, nitric oxide, tumor necrosis factor-α (TNF-α) and mitogen-activated protein kinases.
RESULTS: Steatotic livers preserved in IGL-1® solution supplemented with IGF-1 showed lower transaminase levels, increased bile clearance and a reduction in vascular resistance when compared to those preserved in IGL-1® solution alone. These benefits are mediated by activation of AKT and constitutive endothelial nitric oxide synthase (eNOS), as well as the inhibition of inflammatory cytokines such as TNF-α. Mitochondrial damage and oxidative stress were also prevented.
CONCLUSION: IGL-1® enrichment with IGF-1 increased fatty liver graft preservation through AKT and eNOS activation, and prevented TNF-α release during normothermic reperfusion.
